|Year : 2018 | Volume
| Issue : 2 | Page : 70-74
Assessment of normal range of thyroid function tests in healthy Egyptian pregnant women
Nermin Ahmed Sheriba, Nesma Ali Ibrahim, Nagwa Roshdy Mohamed, Ahmed Magdy Hegab
Department of Endocrinology, National Institute of Diabetes and Endocrinology, Cairo, Egypt
|Date of Web Publication||17-Jul-2018|
Nagwa Roshdy Mohamed
Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Background: Gestational thyroid dysfunction has been associated with a variety of adverse pregnancy outcomes. This study aimed to determine trimester-specific reference intervals of thyroid function tests for normal pregnant Egyptian women.
Subjects and Methods: A cross-sectional study was conducted at the Obstetric Clinic, Ain Shams University Hospitals. The total enrolled pregnant women were 360, who were divided into the following three groups according to gestational age: Group 1 included 120 participants in the first trimester; Group 2 included 120 participants in the second trimester; and Group 3 included 120 participants in the third trimester. All women were healthy with uncomplicated single intrauterine gestations. A detailed obstetric history, clinical examination, estimation of thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies, and thyroglobulin antibodies were done for all participated women.
Results: TSH value increased with advancing pregnancy from 1.43 ± 1.16 μIU/mL in the first trimester to 1.78 ± 1.19 μIU/mL in the third trimester, and the difference between each trimester was statistically significant. The FT4 level decreased from 1.16 ± 0.23 ng/dL in the first trimester to 0.98 ± 0.17 ng/dL in the third trimester, and the difference was statistically significant. The FT3 level decreased from 3.18 ± 0.52 pg/ml in the first trimester to 2.79 ± 0.38 pg/ml in the third trimester, and the difference was statistically significant.
Conclusion: There were significant changes of thyroid function test during each trimester of pregnancy, the reference ranges in this study are different from previous studies outside Egypt. Accordingly, it is necessary to use trimester specific reference range for every population.
Keywords: Pregnancy, reference intervals, thyroid function testing, trimester
|How to cite this article:|
Sheriba NA, Ibrahim NA, Mohamed NR, Hegab AM. Assessment of normal range of thyroid function tests in healthy Egyptian pregnant women. Thyroid Res Pract 2018;15:70-4
|How to cite this URL:|
Sheriba NA, Ibrahim NA, Mohamed NR, Hegab AM. Assessment of normal range of thyroid function tests in healthy Egyptian pregnant women. Thyroid Res Pract [serial online] 2018 [cited 2018 Aug 14];15:70-4. Available from: http://www.thetrp.net/text.asp?2018/15/2/70/236702
| Introduction|| |
During pregnancy, profound changes in the thyroid physiology occur to provide sufficient thyroid hormone (TH) to both the mother and fetus. This supply of TH to the fetus as well as increased concentrations of TH-binding proteins (thyroxine-binding globulin) and degradation of TH by placental type 3 iodothyronine deiodinase necessitates an increased production of maternal TH., Human chorionic gonadotropin (hCG) have similar alphasubunit to thyroid-stimulating hormone (TSH) and a unique betasubunit. As a result, hCG can stimulate the thyroid gland during the first trimester. As a consequence, serum free thyroxine (FT4) concentrations increase and TSH concentrations decrease from approximately the 8th week throughout the first half of pregnancy, resulting in different reference intervals for TSH and FT4 compared to the nonpregnant state.
Thyroid dysfunction during pregnancy is common, with a prevalence of 2%–4%., Maternal thyroid dysfunction is associated with an increased risk of various adverse maternal and child outcomes, including miscarriage, intrauterine growth retardation, hypertensive disorders, and preterm delivery., Given these pregnancy-related changes in the thyroid physiology and the complications associated with thyroid dysfunction, it is important to determine reference intervals for normal thyroid function during pregnancy. This is crucial to identify women who would potentially benefit from treatment. As ethnic background can play a role in both the prevalence of thyroid disease and the establishment of reference intervals, reference range was studied extensively across various countries and also American Thyroid Association (ATA) had published their guidelines.,,,,,,,,, This study aimed to determine trimester-specific reference intervals of the thyroid functions in the normal pregnancies of Egyptian women.
| Subjects and Methods|| |
This was a cross-sectional study that was conducted at the Obstetric Clinic, Ain Shams University Hospitals. Healthy women with uncomplicated single intrauterine gestations in any trimester were consecutively recruited. A detailed obstetric history such as duration of gestation, parity, and number of abortions and also history related to any thyroidrelated illness were obtained. Physical examination included anthropometry, thyroid gland examination, and general and systemic examinations.
A total of 360 women were enrolled in this study. Women were categorized into the following three groups according to gestational age: Group 1 included 120 participants in the first trimester (was considered from weeks 1 to 12); Group 2 included 120 participants in the second trimester (was considered from weeks 13 to 27); and Group 3 included 120 participants in the third trimester (was considered from weeks 28 to 40). For the first trimester, gestational age was calculated using ultrasound and crown-rump length. In the second and third trimesters, the gestational age was established based on the last menstrual period and ultrasound.
Women with the following criteria were excluded:
- History of hyperemesis gravidarum and thyroid illness or use of medication known to affect thyroid functions such as amiodarone, lithium, steroids, and nonsteroidal anti-inflammatory drugs
- Multiple pregnancies
- The family history of thyroid illness
- The presence of more than mild goiter on clinical ground
- Overt hypothyroidism or hyperthyroidism
- Women with significant acute or chronic diseases were also excluded, leaving only healthy or apparently healthy pregnant women to participate in this study
- Women whose specimens were positive for thyroid peroxidase antibodies (TPO-Ab) and/or thyroglobulin antibodies (TG-Ab).
Thyroid function tests (FT3, FT4, and TSH) were performed in Chemical Pathology Unit, Ain Shams University Hospitals on ELISA Reader Stat Fax–2100 using Enzyme Immunoassay Kits supplied by DRG International Inc., USA. The normal ranges of serum hormone concentrations: FT3 = 1.2–4.4 pg/ml, FT4 = 0.8–2 ng/dl, and TSH = 0.5–5 mIU/L.
Estimation of anti-TPO-Ab was done using Elecsys 2010 Immunoassay autoanalyzer (Roche Diagnostics) by electrochemiluminescence immunoassay. Normal range was 0–35 IU/ml. So, values >35 IU/ml were considered positive.
Estimation of anti-TG-Ab was done using the DRG-Anti-thyroglobulin ELISA kit (DRG International Inc., USA). Normal range is 0–100 U/ml. Hence, values >100 U/ml were considered positive.
Specimens positive for TPO-Ab and/or TG-Ab were excluded from the study.
Each woman included in this study was sampled once during her pregnancy and was not sampled again throughout the same pregnancy to avoid missing patient follow-up, to enlarge sample size, and to increase sample variety.
The Statistical Package for the Social Science program version 15 was used for analysis of the data. Data were summarized using mean ± standard deviation (mean ± SD) for quantitative and numbers and percentages for categorical variables. An ANOVA test was done to compare the 3 groups. Post hoc test was used to compare the difference between the two groups. Pearson's correlation was used to examine the relationships of the studied parameters. P < 0.05 was considered statistically significant. This study was conducted after approval from the Institutional Ethics Committee. The women were recruited after a prior informed consent.
| Results|| |
Three hundred and eighty Egyptian pregnant women were invited to participate in the study. We excluded 18 women who were positive to anti-TPO antibodies (5%) and 2 women who were overt hypothyroidism (0.5%). A total of 360 pregnant women were included in the final study population. Group 1 included 120 participants in the first trimester, their mean ± SD of age were 25.7 ± 6.0 years, 46 (38.3 %) were primigravida and 74 (61.7 %) were were multigravida. Group 2 included 120 participants in the second trimester, their mean ± SD of age were 24.4 ± 4.6 years, 52 (43.3 %) were primigravida and 68 (56.7 %) were were multigravida. Group 3 included 120 participants in the third trimester, their mean ± SD of age were 25.5 ± 5.5 years, 61 (50.8 %) were primigravida and 59 (49.2 %) were were multigravida. There was no significant difference between groups regarding age (P = 0.148 ).
TSH level was significantly different between the three groups (P = 0.001). TSH value increased with advancing pregnancy from 1.43 ± 1.16 μIU/mL in the first trimester to 1.64 ± 0.96 μIU/mL in the second trimester and 1.78 ± 1.19 μIU/mL in the third trimester. And, analysis of these parameters between each trimester showed a significant difference. While, FT3 level decreased with the progression of gestational period. It decreased significantly from 1st to 2nd trimester (3.18 ± 0.52 Pg/ml to 2.94±0.41 Pg/ml, P = 0.001), but the decrease from 2nd to 3rd trimester was nonsignificant (2.94 ± 0.41 Pg/ml to 2.79 ± 0.38 Pg/ml, P = 0.11 ). Also, FT4 level decreased with the progression of gestational period. It decreased significantly from 1st to 2nd trimester (1.16 ± 0.23 ng/dL to 1.04±0.16 ng/dL, P = 0.05), but the decrease from 2nd to 3rd trimester was nonsignificant (1.04±0.16 ng/dL to 0.98±0.17 ng/dL, P = 0.10) [Table 1] and [Figure 1].
|Table 1: Comparison of clinical data and thyroid function tests in every trimester (n=360)|
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|Figure 1: The mean value of thyroid function tests during different trimesters. FT3: Free triiodothyronine, FT4: Free tetraiodothyronine, TSH: Thyroid-stimulating hormone|
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The mean ± standard deviation (SD), median and 5th to 95th percentiles for TT3, TT4, and TSH in each trimester of pregnancy are given in [Table 2]. Accordingly, the reference intervals of thyroid function tests for each trimester of our study population are; FT3 2.74 - 3.5 Pg/ml, FT4 0.89 – 1.4 ng/dL, TSH 0.87- 2.42 μIU/mL in the first trimester. FT3 2.66 - 3.27 Pg/ml, FT4 0.85 – 1.18 ng/dL, TSH 0.94- 2.55 μIU/mL in the second trimester. FT3 2.22 – 2.91 Pg/ml, FT4 0.81 – 1.08 ng/dL, TSH 1.44- 2.71 μIU/mL in the third trimester.
| Discussion|| |
During pregnancy, many physiological changes occur, which consequently may affect the normal values of the most widely used thyroid function test parameters. In different geographical areas, a study of the thyroid function tests has been done with different values of the normal reference range, revealing that nearly every population may have unique normal values. There are many trimester-specific reference range studies among the literature. However, the comparison between the studies is not an easy task mostly due to using different laboratory methods for estimation of the thyroid hormones and also due to different inclusion and exclusion criteria. Hence, this study aimed to evaluate the normal values of thyroid function test in pregnancy for the first time in Egypt.In this study, by tracking the TSH mean value for each trimester, we noticed that the TSH value in the first trimester (1.43 ± 1.16 μIU/ml) is lower than in the second trimester (1.64 ± 0.96 μIU/ml) while the third trimester (1.78 + 1.19 μIU/ml) has the highest value during pregnancy. The initial decrease in TSH value is likely due to hCG with its TSH mimetic effect that is characteristic in early pregnancy. With fading up of hCG effect with advancing pregnancy, TSH concentration starts to rise to reach its highest concentration in late pregnancy. This upward sloping curve in the TSH level was also observed by Glinoer et al. as well as by other studies done in Malaysia and China. The reference range of TSH in the second trimester was narrower than those in the first and third trimesters. The ATA suggested that trimester-specific TSH values should be used in every population. When trimester-specific reference intervals are not available, the following reference intervals can be used as follows: the first trimester, 0.1–2.5 μIU/L; the second trimester, 0.2 3.0 μIU/L; and the third trimester, 0.3–3.0 μIU/L.
In this study, the mean value of FT4 showed progressive decline from the first trimester to the third trimester. This was an expected finding where the increased binding of the thyroid hormones to the increasingly produced thyroxin-binding globulin makes the free form to be reduced with advancing pregnancy. The lack of standardizations of free TH measurements makes it difficult to apply a universally accepted standard reference value for it. Thus, it was necessary to develop our own normal values.
The upper limit of the reference range of free T4 in this study was persistently lower than that suggested for normal population range 0.8–2.0 ng/dL, This finding is consistent with a study from Iraq as shown by Moon et al. Iran data on a trimester-specific reference ranges for TSH what was described by Mehran et al. were 0.2–3.9, 0.5–4.1 and 0.6–4.1 μIU/mL for first, second, and third trimesters, respectively. In India, the TSH reference intervals for the first, second, and third trimesters were 0.25–3.35, 0.78–4.96, and 0.9–4.6 μIU/mL, respectively, while for FT4, they were 0.64–2.0, 0.53–2.02, and 0.64–1.99 ng/dL. The Indian study was similar to ours as it used the ELISA technique for estimation of thyroid-related hormones and differs from ours as they excluded pregnant women with previous spontaneous abortion. Our derived TSH reference interval was less than that reported by Dashe et al. (0.01–4.05 μU/mL). However, most of the women in that study were Hispanic.
Although most changes in the thyroid function occur during the first trimester of pregnancy, we wanted to determine whether there were any significant changes observed during the course of the second and third trimesters. Our data showed trimester specific reference range of thyroid function testes that are different from the previous studies outside Egypt and the reference kit ranges. It is therefore crucial that institutions do not rely on fixed universal cutoff concentrations, but calculate their own pregnancy-specific reference intervals. The importance of using correct reference intervals is underlined by the fact that even small subclinical variations in thyroid function have been associated with detrimental pregnancy outcomes including low birth weight and pregnancy loss. Overt hypothyroidism is regarded as a major risk factor for complications of pregnancy and neurocognitive deficits in the developing fetus. ATA supports the use of assay-specific, trimester-specific reference intervals to define thyroid dysfunction during pregnancy.,
Our results showed that TSH levels increased while both FT3 and FT4 levels decreased with progression of gestational age, however, the decrease from second to third trimester was not significant for both. This agreed with Rajput, et al. who found that mean TSH increased and mean FT3 decreased significantly with the progression of gestational period, but FT4 decreased from the first to the third trimester, but the decrease was nonsignificant from the second to the third trimester.
Furthermore, this higher TSH value in the third trimester coincides with Kannan and Kalra  who found that the 95th percentile for TSH in the third trimester, for example, is 1.93 mIU/ml in Manipur, 4.64 mIU/ml in Haryana, 4.60 mIU/ml in West Bengal, and 5.70 mIU/ml in New Delhi.
| Conclusion|| |
There are significant differences of thyroid function test during each trimester of pregnancy, the reference ranges in this study are different from previous studies outside Egypt. These differences can be explained by variations in assays as well as population-specific factors, such as ethnicity and nutrition. Accordingly, it is necessary to use trimester specific reference range for every population. By this study we tried to establish thyroid hormone status in in each trimester in normal pregnant Egyptian women. However, we recommend further larger studies with larger different areas from Egypt are needed to establish normal reference of thyroid hormone in normal pregnant Egyptian women
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Glinoer D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010;31:702-55.
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al.
Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N
Engl J Med 1999;341:549-55.
Chan S, Boelaert K. Optimal management of hypothyroidism, hypothyroxinaemia and euthyroid TPO antibody positivity preconception and in pregnancy. Clin Endocrinol (Oxf) 2015;82:313-26.
Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ 2014;349:g4929.
Soldin OP, Soldin D, Sastoque M. Gestation-specific thyroxine and thyroid stimulating hormone levels in the United States and worldwide. Ther Drug Monit 2007;29:553-9.
Stricker R, Echenard M, Eberhart R, Chevailler MC, Perez V, Quinn FA, et al.
Evaluation of maternal thyroid function during pregnancy: The importance of using gestational age-specific reference intervals. Eur J Endocrinol 2007;157:509-14.
Solberg HE. The IFCC recommendation on estimation of reference intervals. The RefVal program. Clin Chem Lab Med 2004;42:710-4.
Geffré A, Friedrichs K, Harr K, Concordet D, Trumel C, Braun JP, et al.
Reference values: A review. Vet Clin Pathol 2009;38:288-98.
Clinical and Laboratory Standards Institute. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline. Third Edition. CLSI document C28-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
Poulsen OM, Holst E, Christensen JM. Calculation and application of coverage intervals for biological reference values. Pure Appl Chem 1997;69:1601-11.
Harris EK, Boyd JC. Statistical Basis of Reference Values in Laboratory Medicine. New York: Marcel Dekker; 1995.
McLachlan SM, Rapoport B. Breaking tolerance to thyroid antigens: Changing concepts in thyroid autoimmunity. Endocr Rev 2014;35:59-105.
Bestwick JP, John R, Maina A, Guaraldo V, Joomun M, Wald NJ, et al.
Thyroid stimulating hormone and free thyroxine in pregnancy: Expressing concentrations as multiples of the median (MoMs). Clin Chim Acta 2014;430:33-7.
Gilbert RM, Hadlow NC, Walsh JP, Fletcher SJ, Brown SJ, Stuckey BG, et al.
Assessment of thyroid function during pregnancy:First-trimester (weeks 9-13) reference intervals derived from Western Australian women. Med J Aust 2008;189:250-3.
Robinson HP, Fleming JE. A critical evaluation of sonar “crown-rump length” measurements. Br J Obstet Gynaecol 1975;82:702-10.
Sriphrapradang C, Pavarangkoon S, Jongjaroenprasert W, Chailurkit LO, Ongphiphadhanakul B, Aekplakorn W, et al.
Reference ranges of serum TSH, FT4 and thyroid autoantibodies in the Thai population: The national health examination survey. Clin Endocrinol (Oxf) 2014;80:751-6.
Almomin AM, Mansour AA, Sharief M. Trimester-specific reference intervals of thyroid function testing in pregnant women from Basrah, Iraq using electrochemiluminescent immunoassay. Diseases 2016;4. pii: E20.
Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A, et al.
Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 1990;71:276-87.
Zhang J, Li W, Chen QB, Liu LY, Zhang W, Liu MY, et al.
Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ dxI 600. Clin Chem Lab Med 2015;53:1409-14.
Stagnaro-Green A, Abalovich M, Alexander E, Surks MI, Ortiz E, Daniels GH, et al
. Guide lines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081-125.
Moon HW, Chung HJ, Park CM, Hur M, Yun YM. Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women. Ann Lab Med 2015;35:198-204.
Mehran L, Tohidi M, Sarvghadi F, Delshad H, Amouzegar A, Soldin OP, et al.
Management of thyroid peroxidase antibody euthyroid women in pregnancy: Comparison of the American thyroid association and the endocrine society guidelines. J Thyroid Res 2013;2013:542692.
Maji R, Nath S, Lahiri S, Saha Das M, Bhattacharyya AR, Das HN, et al.
Establishment of trimester-specific reference intervals of serum TSH & FT4 in a pregnant Indian population at North Kolkata. Indian J Clin Biochem 2014;29:167-73.
Dashe JS, Casey BM, Wells CE, McIntire DD, Byrd EW, Leveno KJ, et al.
Thyroid-stimulating hormone in singleton and twin pregnancy: Importance of gestational age-specific reference ranges. Obstet Gynecol 2005;106:753-7.
Hirsch D, Levy S, Nadler V, Kopel V, Shainberg B, Toledano Y, et al.
Pregnancy outcomes in women with severe hypothyroidism. Eur J Endocrinol 2013;169:313-20.
Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, et al.
Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003;13:3-126.
Rajput R, Singh B, Goel V, Verma A, Seth S, Nanda S, et al.
Trimester-specific reference interval for thyroid hormones during pregnancy at a tertiary care hospital in Haryana, India. Indian J Endocrinol Metab 2016;20:810-5.
Kannan S, Kalra S. Normative trimester-specific thyroid function data from India: The state of the nation. Indian J Endocrinol Metab 2018;22:5-6.
[Table 1], [Table 2]